Interleukin 5 (IL‐5) and Its Receptor

Abstract

The antibody response to infectious microbes is regulated by a series of interaction among T cells, B cells, and macrophages. Each B cell is genetically determined to maturate antibody (immunoglobulin, Ig)-producing cells against a distinct antigenic determinant on an infectious microbe, and the antibody produced plays a key role in the Immoral immune response against invading microorganisms. The B cell response to an antigen is regulated by a helper T cell responding to, and specific for, the same antigen molecule. Helper T cells recognize antigenic peptides in context of class II major histocompatibility complex (MHC) molecules on B cells, and secrete several soluble factors which can induce growth and maturation of B cells (23,28,36). IL-5 was initially described as a factor that induces terminal differentiation of already activated murine B cells into Ig-secreting cells and originally designated as T-cell-replacing factor (TRF) (56,65).The establishment of a TRF-producing T-cell hybrid B151K12 (B151) which does not secrete detectable levels of other lymphokines affecting B cells demonstrated that TRF is a lymphokine distinct from IL-1, IL-2, IL-3, IL-4, IL-6, and interferon-gamma (IFN-r) (63, 64). TRF produced by B151 was purified to homogeneity and shown to promote DNA synthesis of murine chronic B cell leukemic cells, BCL1 or of dextran sulfate-stimulated normal B cells, and this activity of TRF is called B-cell growth factor (BCGF) II activity (17, 58).We prepared rat anti-mouse TRF mAb (TB13 and NC17) by using HPLCpurified B151-TRF as irnmunogens (18). Both TB13 and NC17 mAbs blocked biological activity of B151-TRF on B cells and BCL1 cells, whereas they did not inhibit biological activities of other cytokines. B151-TRF was purified by using TB 13-coupled immunoaffinity column and found to have an approximate molecular mass of 46 kDa under nonreducing conditions and of 23 to 26 kDa under reducing conditions on SDS-PAGE analysis, indicating that B151-TRF comprises a dimer form.The molecular cloning of complementary DNA (cDNA) encoding murine TRF has convincingly demonstrated that a single molecule is responsible for both TRF and BCGFII activities (27,42). Although TRF was initially believed to be principally active on B cells, recombinant TRF/BCGFII has been shown to be active on T cells and eosinophil progenitors as well as mature eosinophils (42,66, 77). We therefore proposed that TRF/BCGFII be called 59 3

Multiple roles of Lyn kinase in myeloid cell signaling and function

“…Surprisingly, despite the fact that Lyn exerts mainly a negative role in the modulation of other myeloid cell‐type responses to their specific growth factors, Lyn functions as a positive regulator of IL‐5‐induced responses in eosinophils (). IL‐5 receptor has two subunits, the ligand‐specific α subunit and the β subunit which is in common with the IL‐3 receptor and GM‐CSF receptor (101). Lyn associates with IL‐5 receptor α subunit under basal conditions and phosphorylates both the IL‐5 receptor α and β subunits in vitro (102).…”

Cytokines Involved in B-Cell Differentiation and Their Sites of Action

“…These include TRF, BCGFII, BSF-2, and IL-2. The cDNAs for three distinct BSFs were then cloned: (i) IL-4 (73,74), which causes B-cell activation, growth, and differentiation; (ii) IL-5 (75,76), which induces B-cell growth and differentiation with diverse activities; and (iii) IL-6 (77), which induces differentiation of B cells without inducing cell proliferation. Studies of IL-4 revealed that a single cytokine exerts a variety of activities on diverse target cells (78).…”

Lyn Tyrosine Kinase Is Important for IL-5-Stimulated Eosinophil Differentiation

“…The IL-5R has two subunits, the ligand-specific ␣ subunit and the ␤c subunit, which is common to receptors for IL-3 and GM-CSF (10). The signal transduction mechanism of the ␤cR has previously been studied.…”